Subclinical Infections and Male Infertility

S andro C . Esteves, MD., PhD.Director, ANDROFERT

Andrology & Human Reproduction C linic

C ampinas, BRAZIL

S ubclinical Infections and Male Infertility

IS O 9001:2008

Reproductive Andrology S urgery Workshop IIReproductive Medicine Unit - J ahra Hospital - Kuwait 2014

S ubclinical Male G enital Tract Infection (MAG I)

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ANDROLOGY AND HUMAN REPRODUCTION C LINIC - REFERRAL C ENTER FOR MALE REPRODUCTIONS ESTEVES, 22014 December

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Urethritis, prostatitis

MacrophageNeutrophils

ROS production by leukocytes is 100x higher than defective sperm



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C hemical species with unpaired electron capable to oxidize lipids, proteins and nucleic acids:

S uperoxide anion (•O-2)Hydroxyl radical (•OH); Hydrogen peroxide(H2O2)Peroxyl radical (ROO•); Hypochlorite ion (OC l-)

G enerated from sperm aerobic metabolism and leukocytes

Reactive Oxygen S pecies (ROS )

S perm and S eminal Plasma Antioxidants:Enzymatic (S OD, catalase, G PX): inactivate ROS by conversion into

other substancesNon-enzymatic (ascorbic acid, alpha-tocopherol, carnitine, etc):

neutralize ROS



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Yanushpolsky et al 1996, Saleh & Agarwal 2002, Aziz et al 2004


ANDROLOGY AND HUMAN REPRODUCTION C LINIC - REFERRAL C ENTER FOR MALE REPRODUCTIONS ESTEVES, 52014 APRIL

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25%34% 39%

% DNA Damage (SCSA)

Anti-bacterial properties (Zinc)

S emen C ulture Unreliable



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Leukocytospermia>1.0 x 106 leukocytes per mL of semen

marker of reproductive tract inflammation

S pontaneous resolution in 50% of cases

Branigan et al 1995, Erel et al 1997, Lackner et al 2008



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granulocyte macrophage lymphocyte



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Round cells Neubauerchamber

15 minutes

Peroxidase Positive

Peroxidase Negative

20 μl semen + 20μl PBS + 40 μl benzidine + H2O2 solution

• Yanushpolsky et al, 1995; Erel et al. , 1997

• Branigan et al. , 1995Antibiotics

• Lackner et al. , 2006

• G ambera et al. , 2007C icloxigenase-2

Inhibitors

• Oliva & Mutigner, 2006Antihistamines

• Tremellen et al. , 2007

• Piombini et al. , 2008Antioxidants

Treatment of S ubclinical MAG I and Associated Inflammatory C hanges



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S ubclinical MAG I

Azitromycin 1.0g single dose (couple) + frequent ejaculation (every 2-3 days) + Antioxidants

42% leukocytospermia resolution (N=278; Androfert)



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Neisseria gonorrheaeC hlamydia pneumoniaeC hlamydia trachomatisMycoplasma pneumoniaeUreaplasma urealyticum

Max

Min

75th %

25th %

Median

-10

10

30

50

70

90

110

LEUCO_PR

LEUCO_PO

MOT_PRE

MOT_POS

MORF_PRE

MORF_POS

VIT_PRE

VIT_POS

P=0.001

P=0.04

P=0.50

P=0.58

Azitromycin 1.0g single dose (couple) + frequent ejaculation (every 2-3 days)



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MAG I - C linical Management

Ascorbic acid (Vit. C )

- tocopherol (Vit. E)

G lutathione

N-acetyl-cysteine

C arnitine, C oenzyme Q10

Lycopene. Picnogenol

Pentoxifylline. S elenium

S hao-Fu-Zhu-Yu-Tang

Astaxanthin

Lepidium meyenii

-linolenic acid and lignans

Folic acid, Zinc

C ombine OA

Antibiotics

First line therapy

Varicocele

G enital Infection

S moking

Medication

Drug abuse

S ystemic diseases

Pollution

Radiation

Focus on identifying source of increased

ROS



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Oral Antioxidants

How I prescribe

Vitamin C 500mg; Vitamin E 400 mgFolic acid 2 mg; Zinc 25 mgS elenium 26 mcg

Minimum 2 months

Old concept ~80 days

New concept ~60 days

From initiation of sperm production to ejaculation

Misell LM et al. J Urol. 2006

Esteves & Agarwal. Novel concepts in male infertility. Int Braz J Urol 2011



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Outcome No. studies Effect size (OR; 95% C I)

Live birth 3 4.85 [1.92, 12.24]

Pregnancy rate 15 4.18 [2.65, 6.59]

DNA fragmentation 1 -13.80 [-17.50,-10.10]

Miscarriage, sperm count, sperm motility

6-16 No effect

Oral Antioxidants

Showell MG et al. Cochrane Database Syst Rev 2011



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MAG I may decreases fertility mainly via oxidative stress effects

Antibiotic therapy is suggested, but effect on fertility is still unclear (G R-B)

EAU guidelines in male infertility 2014

MAG I Key Messages



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Thank you Obrigado شكرا

Health & Medicine

Subclinical Infections and Male Infertility